N, o-dicarbamoylhydroxylamines



United States Patent 3,192,261 N,O-DICARBAMOYLHYDROXYLAMENES Kathryn Alice Losee and Jack Bernstein, New Brunswick,

N.J., assignors to Olin Mathieson Chemical Corporation, New York, N .Y., a corporation of Virginia No Drawing. Filed July 29, 1963, Ser. No. 298,466

12 Claims. (Cl. 260-545) This invention relates to dicarbamoylhydroxylamines of the formula RNH-! IIO('iNH-R R, R and R in the above formula each represents hydrogen or alkyl, and preferably lower alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl and the like.

The new compounds of this invention may be produced by one of the following methods. When R and R are the same alkyl group, hydroxylamine or an N-alkyl hydroxylamine is reacted with an alkyl isocyanate, RN=(:O. When R and R are ditferent, an appropriately substituted hydroxyurea or O-carbamoylhydroxylamine is reacted with an alkyl isocyanate or cyanic acid. When R, R and R are all hydrogen, hydroxyurea is reacted with an alkali metal cyanate such as potassium cyana'te.

The new compounds of Formula I are useful as antibacterial agents, e.g., to combat such organisms as Proteus vulgaris and Pseudomonas aeruginosa.

The following examples are illustrative of the invention. All temperatures are expressed in degrees centigrade.

EXAMPLE 1 N ,O-dicarbamoy lhydroxy lam ine To a solution of 2.38 grams of hydroxyurea and 10 grams of potassium cyanate in 30 ml. of water, there is added 100 ml. of 0.5 N sulfuric acid, over a period of one hour, during which time the temperature of the reaction mixture is maintained at After two hours at room temperature, the reaction mixture is again cooled to 5 and 100 ml. of 0.5 N sulfuric acid added over a period of one hour. The solution is then deionized by treatment with ion-exchange resin. The filtrate from this treatment is lyophilized and recrystallized from absolute alcohol to give N,O-dicarbamoylhydroxylamine, melting at 158-460.

EXAMPLE 2 N ,0-bis(methylcarbamoyl hydroxylamine- A mixture of 13.8 grams of hydroxylamine hydrochloride and 27.6 grams of potassium carbonate is intimately mixed in a mortar and then suspended in 60 ml. of ether containing 1% water. With vigorous stirring there is then added a solution of 11.4 g. of methyl isocyanate in 50 ml. of ether. After about 15 minutes a crystalline solid begins to precipitate in the reaction mixture, which is stirred for four hours at room temperature. The mixture is then filtered and the dry solid extracted with 100 ml. of absolute alcohol. The alcohol is then removed by distillation under reduced pressure. The solid residue is crystallized from acetonitrile to give the pure product, melting at 13S-136 with decomposition.

EXAMPLE 3 O-carbamoyl-N-methylcarbam'oy[hydroxylamine To a suspension of 1.52 g. of O-carbamoylhydroxylamine in 300 ml. of anhydrous ether at 35, there is added with vigorous stirring a solution of 1.14 g. of methyl isocyanate in ml. of anhydrous ether. An almost clear "ice solution forms, and then a fine precipitate forms in the reaction mixture. The reaction mixture is stirred overnight at room temperature and is then filtered to yield the product which is recrystallized from absolute alcohol, melting at 129-131".

EXAMPLE 4 N ,0-bis(ethylcarbamoyl -N -methylhydr0xyiamine Following the procedure of Example 2 but substituting 16.6 grams of N-methylhydroxylamine hydrochloride for the hydroxylamine hydrochloride and 14.2 grams of ethyl isocyanate for the methyl isocyanate, there is obtained N,O-bis (ethylcarbamoyl) -N-methylhydroxylamine.

EXAMPLE 5 O-n-b utylcarbamoy l-N-carbamoylhyaroxylamine To a solution of 7.6 grams of hydroxyurea in dimethylacetamide there is added dropwise 9.9 grams of n-butyl isocyanate. There is an exothermic reaction and the temperature of the reaction mixture rises from 26 to 48. The reaction mixture is then stirred for one hour to complete the reaction and the product recovered by removal of the dimethylacetamide under reduced pressure.

EXAMPLE 6 O-n-butylcarbam oyl-N-carbamoy l-N-ethylhydroxylamine Following the procedure of Example 5 but substituting 10.4 grams of l-ethyl-l-hydroxyurea for the hydroxyurea there is obtained O-n-butylcarbamoyl-N-carbamoyl- Nethylhydroxylamine.

EXAMPLE 7 O-n-butyloarlmmoyl-N-ethyllcarbamoyll-N- methylhydroxylamine' Following the procedure of Example 5 but substituting 11.8 grams of 1-methyl-3-ethyl-1-hydroxyurea there is obtained O-n-butylcarbamoyl-N-ethylcarbamoy1-N-methylhydroxylamine.

EXAMPLE 8 N ,O-alicarbamoyl-N -mefhylhydroxylamine Following the procedure of Example 1 but substituting 2.7 grams of l-methyl-l-hydroxyurea for the hydroxyurea, there is obtained N,O-dicarbamoyl-N-methylhydroxylamine.

EXAMPLE 9 N -m ethylcarbamoyl-oacarbam oyl-N m'ethylhydrioxyl'amine 0 0 l l lower alkyl-NH- NH- O- -NH-lower alkyl 3. A compound of the formula 4. A compound of {heformula lower 0 alkyl 0 I 1 lower alkyl-NI-I L-N- O- &NH-lower alkyl 5. A compound of the formula ll NH -NHO-C'NH-10wer alkyl 6. A compound of the formula 0 lower alkyl 0 N Hr C-N- OC--NH-loWer alkyl 7. A compound of the formula 10 References Cited by the Examiner Taylor et al.: Organic Chemistry of Nitrogen (1937), pages 288-9.

15 NICHOLAS S. RIZZO, Primary Examiner.

J. D. RANDOLPH, Examiner. 

1. A COMPOUND OF THE FORMULA 